Dyck, P. James B.

ABSTRACTIntroduction: Multifocal motor neuropathy (MMN) is a motor only, asymmetric onset neuropathy that is relatively treatment‐refractory compared with classic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. Methods: We reviewed 35 patients seropositive for GM1 (monosialo‐asialo [immunoglobulin M, IgM; immunoglobulin G, IgG]) and/or GD1b (disialo [IgG, IgM]) autoantibodies having MMN, classic CIDP, or MADSAM. Immune‐treatment responsiveness and clinical course was compared with antibody negative disease controls. Results: Seventy‐nine percent of seropositives with an initial diagnosis of MMN were immunotherapy responsive compared with 46% of seronegatives (P = 0.045). Eight ganglioside antibody positive MMN patients of 19 (42%) developed sensory findings consistent with MADSAM compared with 3 of 41 (7%) seronegative MMN patients (P = 0.003). MMN and MADSAM patients with ganglioside antibody positivity had more sustained treatment responses (P = 0.03). Discussion: Patients initially diagnosed with MMN seropositive for diverse GM1 autoantibodies appear more likely to have sustained treatment response and evolution to MADSAM. Muscle Nerve 57: 1000–1005, 2018

ABSTRACTIntroduction: In polyradiculoneuropathy‐organomegaly‐endocrinopathy‐monoclonal protein‐skin changes (POEMS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), limb nerve conduction studies (NCSs) are limited in identifying demyelination and in detecting treatment effects in severely affected patients. Blink R1 latency may improve these assessments. Methods: POEMS and CIDP patients who had undergone NCS and blink reflex were identified. Correlations among R1 latency, limb NCS, and neuropathy impairment scores (NIS) were compared. Results: Among 182 patients (124 POEMS, 58 CIDP) who were identified, R1 prolongation (>13 ms) occurred in 64.3% (65.3% POEMS, 62.1% CIDP). R1 prolongation correlated with more severely affected NCS in both POEMS (ulnar CMAP 2.6 mV vs. 4.5 mV, P = 0.001) and CIDP (2.0 mV vs. 6.1 mV, P < 0.001). In severely affected patients (ulnar CMAP ≤0.5 mV [10%:18/182]), R1 (>13 ms) helped establish demyelination. In 31 patients (16 POEMS, 15 CIDP), the R1 latency changes were concordant with NIS changes in 94% of patients with POEMS and 60% of patients with CIDP. Discussion: Blink R1 latencies are valuable in defining demyelination and detecting improvement in severely affected POEMS and CIDP patients. Muscle Nerve 57: E8–E13, 2018

OBJECTIVE Nerve biopsy is useful in the management of neuromuscular disorders and is commonly performed in distal, noncritical cutaneous nerves. In general, these procedures are diagnostic in only 20%–50%. In selected cases in which preoperative evaluation points toward a more localized process, targeted biopsy would likely improve diagnostic yield. The authors report their experience with targeted fascicular biopsy of the brachial plexus and provide a description of the operative technique. METHODS All cases of targeted biopsy of the brachial plexus biopsy performed between 2003 and 2015 were reviewed. Targeted nerve biopsy was performed using a supraclavicular, infraclavicular, or proximal medial arm approach. Demographic data and clinical presentation as well as the details of the procedure, adverse events (temporary or permanent), and final pathological findings were recorded. RESULTS Brachial plexus biopsy was performed in 74 patients (47 women and 27 men). The patients' mean age was 57.7 years. All patients had abnormal findings on physical examination, electrodiagnostic studies, and MRI. The overall diagnostic yield of biopsy was 74.3% (n = 55). The most common diagnoses included inflammatory demyelination (19), breast carcinoma (17), neurolymphomatosis (8), and perineurioma (7). There was a 19% complication rate; most of the complications were minor or transient, but 4 patients (5.4%) had increased numbness and 3 (4.0%) had additional weakness following biopsy. CONCLUSIONS Targeted fascicular biopsy of the brachial plexus is an effective diagnostic procedure, and in highly selected cases should be considered as the initial procedure over nontargeted, distal cutaneous nerve biopsy. Using MRI to guide the location of a fascicular biopsy, the authors found this technique to produce a higher diagnostic yield than historical norms as well as providing justification for definitive treatment.

Abstract BACKGROUND: Intraneural perineuriomas are rare, benign lesions produced by the neoplastic proliferation of perineurial cells. They typically present in adolescents and affect nerves of the limbs. In our experience, we have not encountered a single case of classic intraneural perineurioma at an intradural location. OBJECTIVE: To determine whether intraneural perineuriomas could occur intradurally, given the prevalence of intradural nerve sheath tumors, and explain our findings with an anatomic perspective. METHODS: We retrospectively reviewed the high-resolution magnetic resonance images of 56 patients from an institutional registry of patients with intraneural perineurioma. All cases were analyzed for signs of proximal extension toward spinal nerves, roots, and spinal cord. A literature review was performed. The clinical, radiological, and histopathological features of potential intradural lesions were critically appraised against strict criteria for a diagnosis of classic intraneural perineurioma. RESULTS: Fifteen of 56 (27%) patients with intraneural perineurioma had a proximal localization in the lumbosacral or brachial plexus. Not a single case occurred proximal to the dorsal root ganglia (DRG). One case of trigeminal intraneural perineurioma occurred distal to the gasserian ganglion. A literature review did not reveal any convincing cases of classic intraneural perineuriomas occurring in an intraspinal intradural location and revealed only 1 possible case in an intracranial intradural location. CONCLUSION: Based on our study, the occurrence of classic intraneural perineuriomas intradurally is exceedingly rare, if at all present. This may be related to the paucity of perineurial cells at the nerve root level and reciprocal interactions between neuroglial cells at the central-to-peripheral transition zones.

ABSTRACTIntroductionPolyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial.MethodsWe assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis) and its subscores and correlation with disability and health scores.ResultsThe mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests.ConclusionsSpecially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis, broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901–911, 2017

Intraneural perineuriomas are benign peripheral nerve sheath tumors that cause progressive debilitating focal extremity weakness. The etiology of perineuriomas is largely unknown. We utilized whole exome sequencing, copy number algorithm evaluation, and high‐resolution whole genome microarray to investigate for a genetic causal link to intraneural perineuriomas. Ten of 16 (60%) tumor cases had mutations in the WD40 domain of TRAF7, the same location for causal mutations of meningiomas. Two additional perineurioma cases had large chromosomal abnormalities in multiple chromosomes, including chromosome 22q. This study identifies a common cause for intraneural perineuriomas and an unexpected shared pathogenesis with intracranial meningiomas. Ann Neurol 2017;81:316–321

ABSTRACTIntroductionSjögren syndrome is thought to be a lymphocyte‐driven process. Peripheral nervous system involvement occurs in about 20%–25% of patients. A sensory‐predominant, large‐fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation.MethodsWe report a rare case of an acute Sjögren‐associated, sensory predominant, length‐dependent peripheral neuropathy mimicking Guillain–Barré syndrome. The patient presented with sensory ataxia preceded by fever and polyarthralgia. She gave a history of years of dry eyes and dry mouth.ResultsShe had a positive Shirmer test, abnormal salivary gland scan, and positive SS‐A and SS‐B antibodies. A sural nerve biopsy showed an unusual, dense, non‐IgG4, polyclonal, plasma‐cell perivascular infiltrate. The patient responded to treatment with weekly pulse intravenous methylprednisolone.ConclusionsSjögren syndrome can present with acute‐onset, sensory predominant peripheral neuropathy. The role of plasma cells in Sjögren syndrome is unexplored and deserves further study. Muscle Nerve 55: 605–608, 2017